The neuropeptide proctolin (RYLPT) plays important roles as both a neurohormone and a cotransmitter in arthropod neuromuscular systems. We used third-instar Drosophila larvae as a model system to differentiate synaptic effects of this peptide from its direct effects on muscle contractility and to determine whether proctolin can work in a cell-selective manner on muscle fibers. Proctolin did not appear to alter the amplitude of excitatory junctional potentials but did induce sustained muscle contractions in preparations where the CNS had been removed and no stimuli were applied to the remaining nerves. Proctolin-induced contractions were dose-dependent, were reduced by knocking down expression of the Drosophila proctolin receptor in muscle tissue, and were larger in some muscle cells than others (i.e., larger in fibers 4, 12, and 13 than in 6 and 7). Proctolin also increased the amplitude of nerve-evoked contractions in a dose-dependent manner, and the magnitude of this effect was also larger in some muscle cells than others (again, larger in fibers 4, 12, and 13 than in 6 and 7). Increasing the intraburst impulse frequency and number of impulses per burst increased the magnitude of proctolin's enhancement of nerve-evoked contractions and decreased the threshold and EC50 concentrations for proctolin to enhance nerve-evoked contractions. Reducing proctolin receptor expression decreased the velocity of larval crawling at higher temperatures, and thermal preference in these larvae. Our results suggest that proctolin acts directly on body-wall muscles to elicit slow, sustained contractions and to enhance nerve-evoked contractions, and that proctolin affects muscle fibers in a cell-selective manner.
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http://dx.doi.org/10.1152/jn.00606.2015 | DOI Listing |
Am J Physiol Lung Cell Mol Physiol
January 2025
Smooth Muscle Research Centre, Dundalk Institute of Technology, Dublin Road, Dundalk, Co. Louth, Ireland.
Cholinergic tone is elevated in obstructive lung conditions such as COPD and asthma, but the cellular mechanisms underlying cholinergic contractions of airway smooth muscle (ASM) are still unclear. Some studies report an important role for L-type Ca channels (LTCC) and Ano1 Ca-activated Cl™ channels (CACC) in these responses, but others dispute their importance. Cholinergic contractions of ASM involve activation of M3Rs, however stimulation of M2Rs exerts a profound hypersensitisation of these responses.
View Article and Find Full Text PDFFront Physiol
August 2024
dNea Onnim Consultancy, StAugustine, FL, United States.
Introduction: Maximal voluntary isometric contractions (MVICs) as a fatiguing modality have been widely studied, but little attention has been given to the influence of the rate of torque development. Given the established differences in motor command and neuromuscular activation between ramp and rapid MIVCs, it is likely performance fatigue differs as well as the underlying physiological mechanisms.
Purpose: To compare responses for rapid and maximal torque following ramp and rapid MVICs, and the corresponding neuromuscular and corticospinal alterations.
Int J Mol Sci
August 2024
Institute of Preclinical Sciences, Veterinary Faculty, University of Ljubljana, Gerbičeva 60, 1000 Ljubljana, Slovenia.
Cholinesterase (ChE) inhibitors are crucial therapeutic agents for the symptomatic treatment of certain chronic neurodegenerative diseases linked to functional disorders of the cholinergic system. Significant research efforts have been made to develop novel derivatives of classical ChE inhibitors and ChE inhibitors with novel scaffolds. Over the past decade, ruthenium complexes have emerged as promising novel therapeutic alternatives for the treatment of neurodegenerative diseases.
View Article and Find Full Text PDFCell Calcium
November 2024
Smooth Muscle Research Centre, Department of Life & Health Science, Dundalk Institute of Technology, Dundalk, Co. Louth, Ireland; Department of Physiology & Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV, USA. Electronic address:
Urethral smooth muscle cells (USMC) contract to occlude the internal urethral sphincter during bladder filling. Interstitial cells also exist in urethral smooth muscles and are hypothesized to influence USMC behaviours and neural responses. These cells are similar to Kit interstitial cells of Cajal (ICC), which are gastrointestinal pacemakers and neuroeffectors.
View Article and Find Full Text PDFbioRxiv
June 2024
Department of Orthopedics, University of Maryland School of Medicine, Baltimore, MD, USA.
Duchenne muscular dystrophy (DMD) is marked by the genetic deficiency of the dystrophin protein in striated muscle whose consequence is a cascade of cellular changes that predispose the susceptibility to contraction injury central to DMD pathology. Recent evidence identified the proliferation of microtubules enriched in post-translationally modified tubulin as a consequence of dystrophins absence that increases the passive mechanics of the muscle fiber and the excess mechanotransduction elicited reactive oxygen species and calcium signals that promote contraction injury. Motivated by evidence that acutely normalizing the disease microtubule alterations reduced contraction injury in murine DMD muscle (), here we sought the direct impact of these microtubule alterations independent of dystrophins absence and the multitude of other changes consequent to dystrophic disease.
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